Leukocyte Recruitment to Peritoneal Cavity of Rats Following Formalin Injection: Role of Tachykinin Receptors

Abstract

The aim of this work was to verify whether formalin would induce leukocyte recruitment following intraperitoneal (i.p.) injection in rats. Formalin (1.25 – 2.5%) induced cell recruitment, which was concentration- and time-dependent (0 – 24 h). Two peaks of leukocyte recruitment were observed. The first peak (from 2 to 4 h) was characterized by a mixed polymorphonuclear and lymphocyte cell population (representing an increase of 100 – 220% and 55 – 60%, respectively), whereas the second peak was characterized by a marked increase in lymphocytes at 24 h (representing an increase of 230%). Pretreatment of animals with specific antagonists for neurokinin NK1, NK2, and NK3 receptors (SR140333, SR48968, and SR142801 compounds, respectively) reduced the early leukocyte increase (representing a significant reduction of 65%, 51%, and 46%, respectively), whereas only the treatment with NK2-specific antagonist reduced the late cell increase induced by formalin injection (amounting to a significant reduction of 48%). These results suggested that substance P, neurokinin A, and neurokinin B release accounted for formalin-induced cell migratory activity. The anti-inflammatory drug dexamethasone also reduced cell recruitment, which was mainly related to a reduction in 79% of the neutrophils at 4 h following 1.25% formalin injection, suggesting also a release of lipid mediators (eicosanoids and/or platelet-activating factor) and/or cytokines/chemokines by the formalin injection.